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Global Burden

HAT is primarily concentrated in Central Africa; 70% of all infections occur in a single country, Democratic Republic of Congo (DRC). There are a total of 37 countries in sub-Saharan Africa with endemic HAT and an estimated at risk population of nearly 60 million people. A small amount of transmission also occurs in the Eastern Mediterranean Region (<10% of all cases).

According to the World Health Organization (WHO), in 2009 the incidence of new HAT infections dropped below 10,000 cases for the first time in more than 50 years.¹ Due to known underreporting, the actual prevalence of disease is estimated to be closer to 30,000 cases. Between 1999 and 2008, the incidence of chronic and acute disease declined by 62% and 58%, respectively. The severe debilitating effects of HAT, combined with the high mortality rate, result in an estimated 1.7 million DALYs lost per year.

The economic impact of HAT, in combination with zoonotic forms of the disease that affect livestock, has severely impaired agricultural development in Central Africa. It is estimated that Africa loses US$1.5 billion in revenues from agriculture annually due to the combined human and zoonotics forms of sleeping sickness.²

Causative Agent

HAT is caused by the protozoan parasite Trypanosoma brucei. Humans become infected when parasites are injected into the human by the bite of a tsetse fly. The injected parasites can replicate asexually in the blood and invade the lymphatic and central nervous systems. Tsetse flies pick up parasites from the blood of an infected person while taking a blood meal, thus continuing the lifecycle. Unlike the closely related American trypanosome parasite, T. cruzi, T. brucei does not appear to invade cells and convert to the intracellular form known as the amastigote. Although there is some evidence that this transition can occur in T. brucei, it appears to be rare and less significant for disease pathology than in its American cousin.

T. brucei parasites are transmitted through the bite of tsetse flies of the genus Glossina. T. brucei can also be transmitted from mother to child during pregnancy and be mechanically transmitted through blood products. However, the majority of transmission is attributed to the tsetse fly.

Pathogenesis

Two forms of disease exist depending on the parasite sub-species: (1) Gambian or West African sleeping sickness is caused by Trypanosoma brucei gambiense, and (2) Rhodesian, Central, or East African sleeping sickness is caused by Trypanosoma brucei rhodesiense.

Gambian or West African sleeping sickness is the most common form of HAT, accounting for greater than 95% of cases. This form of disease is a chronic infection that begins asymptomatically and may present with non-specific symptoms such as fever and fatigue as parasites invade the lymphatic system (stage 1 disease). If left untreated, parasites can invade the central nervous system resulting in stage 2 disease and death. There is no animal reservoir for T. b. gambiense.

Rhodesian, Central, or East African sleeping sickness is less common, accounting for fewer than 5% of all cases. T. b. rhodesiense infection of humans results in acute infection and rapid progression to stage 2 disease. Rhodesian sleeping sickness is primarily a zoonotic infection with a large animal reservoir. It is likely that humans are only accidental hosts for this parasite.

Current Control Strategy

The current control strategy consists of two parts:

1. Active case detection and treatment
2. Vector control

Early detection of disease is essential for the treatment of HAT. Although treatment for stage 1 disease can be administered at the village level, treatment for stage 2 disease requires hospital administration and supportive care for toxic side effects. However, the non-specific symptoms of stage 1 disease make clinical diagnosis difficult. In areas of known transmission, WHO supports active screening and surveillance methods by providing free reagents, medicines, and support through mobile screening teams. Both serological (T. b. gambienseonly) and parasitological diagnostic methods are used to screen patients. By detecting and treating stage 1 disease, patients can avoid taking the toxic drugs used to treat stage 2 disease and the human reservoir of parasites harbored in asymptomatic patients is reduced.

Vector control is the second key component of HAT control programs. Several strategies are used including tsetse fly traps, introduction of sterile male flies into the environment, and avoidance of known tsetse fly habitats.

Existing Products

Drugs

Treatment of HAT depends on the species of parasite causing the infection and the stage of the disease as summarized below. NECT, a co-administration of nifurtimox and eflornithine, is the first new drug for HAT in over 25 years. Although NECT has not yet been approved by any country’s regulatory agency, it has been added to the WHO essential medicines list and is recommended by the WHO over more toxic melarsoprol for the treatment of stage 2 T. b. gambiense disease.

Vaccines

There are currently no vaccines in use for HAT.

Diagnostics

Diagnosis of HAT is done primarily by microscopy. Both T. b. rhodesiense and T. b. gambiense can be seen in blood smears. A card indirect agglutination test (CATT) is also available for T. b. gambiense. To diagnose stage 2 disease, microscopy is performed on cerebral spinal fluid obtained by lumbar puncture. As the sensitivity of microscopy is not optimal for CSF, staging is usually done with white cell count in CSF to guide treatment. A white cell count of 5 or less is suggestive of stage 1; > or equal to 20 is suggestive of stage 2; in between is indeterminate. An easier method has been developed using rosette formation by binding white cells in the CSF to a CD3 pan marker for white cells.

References

1. WHO African Trypanosomiasis Fact Sheet.
2. WHO (2010) First WHO report on neglected tropical diseases 2010: working to overcome the global impact of neglected tropical diseases.

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